| Literature DB >> 25366541 |
Je-Hyun Yoon1, Supriyo De1, Subramanya Srikantan1, Kotb Abdelmohsen1, Ioannis Grammatikakis1, Jiyoung Kim1, Kyoung Mi Kim1, Ji Heon Noh1, Elizabeth J F White2, Jennifer L Martindale1, Xiaoling Yang1, Min-Ju Kang1, William H Wood1, Nicole Noren Hooten3, Michele K Evans3, Kevin G Becker1, Vidisha Tripathi4, Kannanganattu V Prasanth4, Gerald M Wilson2, Thomas Tuschl5, Nicholas T Ingolia6, Markus Hafner7, Myriam Gorospe1.
Abstract
Post-transcriptional gene regulation is robustly regulated by RNA-binding proteins (RBPs). Here we describe the collection of RNAs regulated by AUF1 (AU-binding factor 1), an RBP linked to cancer, inflammation and aging. Photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP) analysis reveals that AUF1 primarily recognizes U-/GU-rich sequences in mRNAs and noncoding RNAs and influences target transcript fate in three main directions. First, AUF1 lowers the steady-state levels of numerous target RNAs, including long noncoding RNA NEAT1, in turn affecting the organization of nuclear paraspeckles. Second, AUF1 does not change the abundance of many target RNAs, but ribosome profiling reveals that AUF1 promotes the translation of numerous mRNAs in this group. Third, AUF1 unexpectedly enhances the steady-state levels of several target mRNAs encoding DNA-maintenance proteins. Through its actions on target RNAs, AUF1 preserves genomic integrity, in agreement with the AUF1-elicited prevention of premature cellular senescence.Entities:
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Year: 2014 PMID: 25366541 PMCID: PMC4291169 DOI: 10.1038/ncomms6248
Source DB: PubMed Journal: Nat Commun ISSN: 2041-1723 Impact factor: 14.919